Department of Chemistry , Purdue University , West Lafayette , Indiana 47907 , United States.
Department of Analytical Research & Development , Merck & Co., Inc. , Rahway , New Jersey 07065 , United States.
Anal Chem. 2018 Aug 7;90(15):9426-9433. doi: 10.1021/acs.analchem.8b02083. Epub 2018 Jul 23.
Isomeric O- and N-glucuronides are common drug metabolites produced in phase II of drug metabolism. Distinguishing these isomers by using common analytical techniques has proven challenging. A tandem mass spectrometric method based on gas-phase ion/molecule reactions of deprotonated glucuronide drug metabolites with trichlorosilane (HSiCl) in a linear quadrupole ion trap mass spectrometer is reported here to readily enable differentiation of the O- and N-isomers. The major product ion observed upon reactions of HSiCl with deprotonated N-glucuronides is a diagnostic HSiCl adduct that has lost two HCl molecules ([M - H + HSiCl - 2HCl]-). This product ion was not observed for deprotonated O-glucuronides. Reaction mechanisms were explored with quantum chemical calculations at the M06-2X/6-311++G(d,p) level of theory.
O-和 N-葡糖醛酸苷是药物代谢二期反应中常见的药物代谢物。使用常见的分析技术来区分这些异构体一直具有挑战性。本文报道了一种基于在线性四极离子阱质谱仪中用三氯硅烷(HSiCl)与去质子化葡糖醛酸苷药物代谢物进行气相离子/分子反应的串联质谱方法,可轻松区分 O-和 N-异构体。用 HSiCl 与去质子化 N-葡糖醛酸苷反应时观察到的主要产物离子是一种诊断性的 HSiCl 加合物,它失去了两个 HCl 分子([M - H + HSiCl - 2HCl]-)。对于去质子化的 O-葡糖醛酸苷,未观察到该产物离子。使用 M06-2X/6-311++G(d,p)理论水平的量子化学计算探讨了反应机理。